The phosphoinositide phospholipids have unique polar and anionic structures, and are membrane components with a high affinity for calcium ions. Their phosphate incorporation rates increase in response to neurotransmitters and secretogogues, and their involvement in neural and secretory functions has been suggested. In the adrenal medulla the inositides are associated with chromaffin granule membranes and with acetylcholine-stimulated secretion of catecholamines. In the current proposal, the steps of "stimulus-secretion coupling" will be pharmacologically dissected to determine which events are involved with the inositides, and the subcellular loci of inositide involvement will be determined. The endogenous levels, phosphate incorporation rates and subcellular distribution of the individual inositides will be examined under normal and pharmacologically perturbed conditions. These studies will provide information as to the nature of the numerous inositide phenomena reported for secretory tissues, and may suggest a role for the inositides in neurotransmission.